Youssefyeh, Raymond D.; Campbell, H. F.; Airey, J. E.; Klein, S.; Schnapper, M.; Powers, M.; Woodward, R.; Rodriguez, W.; Golec, S. published the artcile< Development of high-affinity 5-HT3 receptor antagonists. 2. Two novel tricyclic benzamides>, Related Products of 120570-05-0, the main research area is serotoninergic S3 antagonist tricyclic benzamide; quinuclidinylaminocarbonyl dibenzofuran derivative preparation antiemetic.
Two new classes of potent 5-HT3 agents have been developed and examined as inhibitors of cytotoxic drug induced emesis in the ferret and dog. The absolute configuration of the most active mols. I and II have been determined by x-ray crystallog. These two compounds are more potent than known 5-HT3 receptor antagonists both in vivo and in vitro in blocking 5-HT3 receptor activation and preventing chemotherapeutic induced emesis. Compared with 5-HT3 antagonists, such as GR 38032F, zacopride, BRL 43694, and ICS 205-930, I was more potent in (1) inhibiting binding to 5-HT3 receptor binding sites in rat cortex (Ki = 0.17 nM), (2) blocking the von Bezold-Jarisch effect in the rat (lowest ED, 1 μg/kg i.v.), and (3) inhibiting 5-HT-induced contraction of guinea pig ileum (lowest effective concentration, 10-9 M). This novel agent was as effective given orally as when given i.v. in reducing cisplatin-induced emetic episodes in the ferret (ED50 = 4 μg/kg i.v. or orally). A 1 mg/kg oral dose of I virtually abolished cisplatin-induced emesis for 10 h in the ferret. However, it was inactive against apomorphine or copper sulfate-induced vomiting. These data, coupled with receptor binding studies of ligands for D2-dopamine, a1, a2, 5-HT1, 5-HT2, and muscarinic receptors demonstrate that II is a highly selective 5-HT3 receptor antagonist with remarkable potency in vivo.
Journal of Medicinal Chemistry published new progress about 5-HT3 antagonists. 120570-05-0 belongs to class quinuclidine, and the molecular formula is C7H14N2, Related Products of 120570-05-0.
Referemce:
Quinuclidine – Wikipedia,
Quinuclidine | C7H13N | ChemSpider